This invention is directed to the treatment of premalignant lesions and malignant tumors. It has been known to utilize the compound 1,2,3,4-tetrahydro-1,1,4,4-tetramethyl-6-(alpha-methylstyryl)naphthalene which has the formula ##STR1## for the systemic and topical treatment or prevention of conditions caused by an increased sebum secretion, such as greasy hair, oily scalp, seborrhea and especially acne vulgaris. See U.S. Pat. No. 4,588,750, Boris, issued May 13, 1986. Prior to its discovery for use in the treatment or prevention of conditions caused by increased sebum secretion, the compound of formula I had been found biologically inactive in preliminary screening tests, see Rydell et al., Acta pharmacol. et toxicol., 51, 413-420 (1982); Kistler, Calcif Tissue Int. 33, 249-254 (1981) and Loeliger et al., Eur. J. Med. Chem.-Chimica Therapeutica, 15, No. 1, 9-15 (1980).
Retinoids play an essential role in controlling the normal differentiation of various tissues and are therefore important for controlling premalignant cell differentiation. It has even been found that retinoids can cause cellular repair of hyperplastic and anaplastic lesions caused by chemical carcinogens. Moreover, retinoid deficiency has been shown, in experimental animals, to enhance susceptibility to chemical carcinogenesis. Indeed, retinoids are essential for the normal cellular differentiation of epithelial cells where more than half of the total primary cancers develop in both men and women. These epithelial cells include the bronchi, trachea, breast, stomach, intestine, uterus, kidney, bladder, testis, prostate, pancreatic ducts and skin. In the absence of retinoids in the diet, normal cellular differentiation does not occur.
The developments in this field, which are summarized above, are discussed in an article entitled "Prevention of Chemical Carcinogenesis by Vitamin A and its Synthetic Analogs (Retinoids)", Federation Proceedings, 35, (May 1, 1976), 1332-1338, in which it is noted that it still remains a goal to find, for practical application to man and other mammals, highly effective synthetic retinoids that also have low toxicity and a high degree of tissue specificity against cancer at any particular organ site. See also the articles in the Fall, 1977, issue of The Southern Research Institute Bulletin (Volume 30, Number 2), pages 3-9 ("CHEMOPREVENTION OF CANCER--Steps Leading to Some Malignancies May Be Reversible" and "How Do Retinoids Work? Studies on Retinoic Acid-Binding Protein"). Other publications of interest in this field include "Biological Activity and Metabolism of the Retinoid Axerophthene (Vitamin A Hydrocarbon)", Cancer Research 38, 1734-1738, June 1978; and "Retinoids and Cancer Prevention: The importance of the Terminal Group of the Retinoid Molecule In Modifying Activity and Toxicity" in Carcinogens: Identification and Mechanism of Action, A. C. Griffin & C. R. Shaw, Editors, N.Y. Raven Press, 1978.
While retinoid-type compounds have been found to be effective in treating carcinomas, and inhibiting the progression of premalignant or precancerous lesions, many of these retinoids have high toxicity and produce deleterious adverse effects such as hypervitaminosis A. The toxicity and adverse effect profile of many of these retinoids make them unsuitable for use in the treatment and prevention of cancer at high dosage levels where their effects are greatest. Therefore, it is desired to provide a retinoid type compound which will exhibit at high dosages the tumor inhibiting effect of retinoids without the toxic manifestation or adverse effects generally associated with such retinoids.